Combined Infusion of Cytotoxic T-Lymphocytes and Vaccination

Complication of Transplant Clinical Trial

— CYNTAX  

Official title:

Combined Infusion of Cytotoxic T-Lymphocytes and Vaccination to Enhance Infection-Specific Immune Reconstitution Post-Allogeneic Stem Cell Transplantation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02843321
• Other study ID #: Cyntax
• Status: Active, not recruiting
• Phase: Phase 1
• First received: May 18, 2016
• Last updated: November 21, 2016
• Start date: August 2012
• Est. completion date: December 2017

Study information

• Verified date: November 2016
• Source: University of Sydney
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial Summary

To assess the safety and biological efficacy of prophylactically administered donor-derived multi-infection specific cytotoxic T lymphocytes (CTLs) (targeting cytomegalovirus (CMV), Adenovirus (Adv), Epstein Barr virus (EBV), Varicella-Zoster virus (VZV), Influenza (Flu), BK virus (BKV), and Aspergillus (Asp)) combined with early immunisation with Influenza and VZV vaccines for the prevention of viral and fungal infection following allogeneic blood or marrow stem cell transplantation.

Description:

The study will analyse the safety and biological efficacy of administering the investigational products (donor-derived T cells stimulated with viral and fungal antigen expressing DC combined with Flu and VZV immunisation), for the prophylaxis of viral and fungal reactivation and/or infection following allogeneic blood or marrow transplantation. The cells will be given prophylactically a minimum of 28 days after transplantation followed by administration of the Flu and VZV vaccines 24 to 72 hours later. The AIMS are to study the safety of combining CTL infusions and vaccination as well as their effect on reconstitution of infection-specific immunity, viral and Aspergillus reactivation and infection rates after transplantation, viral load, and use of antiviral and antifungal pharmacotherapy for specific infections. The investigators will also evaluate the safety of infusions and vaccinations with respect to the development adverse events within the first 12 months post transplant.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 12
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Patients undergoing myeloablative or non-myeloablative allogeneic transplantation from an HLA (A, B and DR) identical or 1-3 antigen mismatched family or unrelated donor.

• Transplant performed for any type of non-malignant condition or haematological malignancy including but not limited to acute and chronic leukaemia, myelodysplasia, non Hodkgins and Hodgkin lymphoma or myeloma.

• Recipients of peripheral blood or bone marrow stem cells.

• Adequate hepatic and renal function (< 3 x upper limit of normal for AST (SGOT), ALT (SGPT), < 2 x upper limit of normal for total bilirubin, serum creatinine).

• Estimated life expectancy of at least 6 months.

• Patient (or legal representative) has given informed consent

Exclusion Criteria:

• Use of anti-lymphocyte globulin (ALG, ATG, Campath or other broad spectrum lymphocyte antibody) given in the 4 weeks immediately prior to infusion or planned within 4 weeks after infusion.

• Grade II or greater graft versus host disease within 1 week prior to infusion.

• Prednisone or methylprednisone at a dose of > 1 mg/kg (or equivalent in other steroid preparations) administered within 72 hours prior to cell infusion.

• Allergies to eggs or components of the Fluvax or Varivax vaccines.

• Privately insured in or outpatients

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Complication of Transplant

Intervention

Biological:
• T-cell infusion, influenza vaccination
Donor derived infection-specific T-cells (with activity against CMV,adenovirus, EBV, VZV, Influenza, BKV and Aspergillus) and vaccination (with Fluvax)

Locations

Country	Name	City	State
Australia	Westmead Hospital Department of Haematology	Westmead, Sydney	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
University of Sydney

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of infection-specific T-cell infusion and vaccination	Presence of acute infusion related toxicities	1 week	Yes
Secondary	Change in infection specific immune reconstitution		1 week, 2 weeks, 3 weeks, 4 weeks, 3 months, 6 months, 9 months, 12 months (post T-cell infusion)	Yes
Secondary	Change in CMV, EBV and BKV load based on quantitive PCR		1 week, 2 weeks, 3 weeks, 4 weeks, 3 months, 6 months, 9 months, 12 months (post T-cell infusion)	Yes
Secondary	Use of specific anti-viral pharmacotherapy		12 months (post T-cell infusion)	Yes
Secondary	Use of systemic anti-fungal drugs including amphotericin and azoles		12 months (post T-cell infusion)	Yes
Secondary	Incidences of GVHD		12 months (post T-cell infusion)	Yes
Secondary	Number of in-hospital days following first discharge post transplant		12 months (post T-cell infusion)	Yes